Cocaine abuse remains a grave concern for the American, and increasingly the world, population. As no current therapeutic agents are available to assist cocaine addicts in achieving and maintaining abstinence it is important that new pharmacotherapies be developed. One important question not usually addressed in the development of new therapies for the treatment of cocaine abuse is the neuroadaptive effects of chronic administration of the pharmacotherapy. Cocaine use and subsequent withdrawal is known to result in profound neuroadaptions, particularly in the monoaminergic transporters. As any therapy that potentiates the changes induced by cocaine would be expected to exuberate the symptoms of withdrawal, it is important to address this question early in any cocaine medication development program. With this in mind we will examine the effects of a novel pharmacotherapy, CTDP 31,446, which has been designated by NIDA as a preclinical development candidate for the treatment of cocaine abuse. We will extend our promising recent findings and examine the neuroadaptive effects of CTDP 31,446 on different monoamine transporters after 7, 14, and 21 days of infusion. Additional experiments will examine the persistence of these adaptations at different time intervals following discontinuation of treatment. PROPOSED COMMERCIAL APPLICATION: Currently there are no proven medications for the treatment of cocaine abuse. The sucessful completion of the work proposed here will ultimately lead to the development and marketing of a drug for the treatment of cocaine addication.